TMUB1 is a transmembrane ubiquitin-like protein with multifaceted roles in cell regulation and immune evasion. Functionally, TMUB1 contributes to translation regulation during cell-cycle progression and centrosome assembly 1. TMUB1 acts as a scaffold protein that interacts with multiple partners: it modulates PD-L1 post-translational modifications by competing with E3 ubiquitin ligase HUWE1 to inhibit PD-L1 polyubiquitination while enhancing its N-glycosylation and stability 2, and it bridges ERLIN scaffolds with RNF170 in ERAD pathways regulating cholesterol transport 3. TMUB1 forms complexes with RNF185 and TMEM259 for quality control of ER membrane proteins 4. Clinically, TMUB1 is significantly overexpressed in multiple tumor types including colorectal, liver, esophageal, and CNS cancers 15. High TMUB1 expression correlates with poor survival and associates with tumor immune evasion by stabilizing PD-L1 25. TMUB1 promotes proliferation by suppressing p19Arf stability 1 and enhances AKT ubiquitination to drive colorectal cancer progression 6. Additionally, TMUB1 serves as a binding partner for IGSF9, activating IL-6/STAT3 signaling to induce tumor-associated macrophage senescence and immunosuppression 7. These findings establish TMUB1 as a promising immunotherapeutic target and prognostic biomarker.